The impact of city-wide deployment of Wolbachia-carrying mosquitoes on arboviral disease incidence in Medellín and Bello, Colombia: study protocol for an interrupted time-series analysis and a test-negative design study

Abstract

Background: Dengue, chikungunya and Zika are viral infections transmitted by Aedes aegypti mosquitoes, and present major public health challenges in tropical regions. Traditional vector control methods have been ineffective at halting disease transmission. The World Mosquito Program has developed a novel approach to arbovirus control using Ae. aegypti stably transfected with the Wolbachia bacterium, which have significantly reduced ability to transmit dengue, Zika and chikungunya in laboratory experiments. Field releases in eight countries have demonstrated Wolbachia establishment in local Ae. aegypti populations. Methods: We describe a pragmatic approach to measuring the epidemiological impact of city-wide Wolbachia deployments in Bello and Medellín, Colombia. First, an interrupted time-series analysis will compare the incidence of dengue, chikungunya and Zika case notifications before and after Wolbachia releases, across the two municipalities. Second, a prospective case-control study using a test-negative design will be conducted in one quadrant of Medellín. Three of the six contiguous release zones in the case-control area were allocated to receive the first Wolbachia deployments in the city and three to be treated last, approximating a parallel two-arm trial for the >12-month period during which Wolbachia exposure remains discordant. Allocation, although non-random, aimed to maximise balance between arms in historical dengue incidence and demographics. Arboviral disease cases and arbovirus-negative controls will be enrolled concurrently from febrile patients presenting to primary care, with case/control status classified retrospectively following laboratory diagnostic testing. Intervention effect is estimated from an aggregate odds ratio comparing Wolbachia-exposure odds among test-positive cases versus test-negative controls. Discussion: The study findings will add to an accumulating body of evidence from global field sites on the efficacy of the Wolbachia method in reducing arboviral disease incidence, and can inform decisions on wider public health implementation of this intervention in the Americas and beyond. Trial registration: ClinicalTrials.gov: NCT03631719. Registered on 15 August 2018.

Molecular Detection of the Endosymbiont <em>Wolbachia </em>sp. in <em>Acanthocheilonema Reconditum </em>and Potential Vectors

“…Likewise, it is an endosymbiont of fleas, which are essential for human and animal health because they are vectors of pathogens, such as Rickettsii typhi, Rickettsia felis, and Bartonella spp., around the world [29][30][31][32][33]. Wolbachia pipientis has been recently proposed as a biocontrol agent to mitigate the reproduction of the A. aegypti mosquito [28], one of the main vectors of diseases such as dengue, chikungunya, zika, and yellow fever [34][35]. The increased impact of these infectious diseases, especially dengue, in Latin America in the last two decades [36] has required the implementation of new control methodologies.…”

“…Aedes aegypti mosquitoes carrying Wolbachia sp. were released in the cities of Bello and Medellín (northwestern Colombia) in 2018 [34] and in Cali in 2019. The purpose of the latter was to reduce the transmission of dengue because Cali accounted for approximately 20% of the total number of cases reported in Colombia in 2016 [37].…”

Current vector research challenges in the greater Mekong subregion for dengue, Malaria, and Other Vector-Borne Diseases: A report from a multisectoral workshop March 2019

“…Additionally, other approaches involve promoting or activating mosquito immune responses against infecting arboviruses that would alter transmission capabilities [105][106][107][108]. Biological control methods, such as Wolbachia infection of A. aegypti, are aimed at reducing the competence of vectors and have reduced dengue incidence in the same areas as field trials in Australia and Indonesia, with documented success in arbovirus control in Colombian releases; and controlled release of Wolbachia-induced sterile males reduced the A. aegypti populations in targeted areas in Florida [109][110][111]. Further, there is interest in the use of endectocides for tackling residual malaria transmission (RMT).…”

“…aegypti , are aimed at reducing the competence of vectors and have reduced dengue incidence in the same areas as field trials in Australia and Indonesia, with documented success in arbovirus control in Colombian releases; and controlled release of Wolbachia -induced sterile males reduced the A . aegypti populations in targeted areas in Florida [ 109 – 111 ]. Further, there is interest in the use of endectocides for tackling residual malaria transmission (RMT).…”

Local-scale virome depiction supports significant differences between Aedes aegypti and Aedes albopictus

“…Thus, these cities were selected for pioneering efforts to test an alternative control strategy based on the release of Wolbachia -transfected Ae. aegypti mosquitoes, which started in 2017 [34]. These releases have not yet provided any conclusive epidemiological evidence of arboviruses control in Medellín.…”